Chemical Name: α-L-iduronate sulfate sulfatase
Molecular Formula: C2689H4057N699O792S14
CAS Number: 50936-59-9
- Risk of Anaphylaxis
Life-threatening anaphylactic reactions observed in some patients during idursulfase infusions. Appropriate medical support should be readily available.
Biphasic anaphylactic reactions also observed after administration. Patients who experienced anaphylactic reactions may require prolonged observation.
Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions; may require additional monitoring.
Biosynthetic (recombinant DNA origin) form of human iduronate-2-sulfatase; lysosomal enzyme that catalyzes the hydrolysis of the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate.1 2 4 5 6 7
Uses for Idursulfase
Management of Hunter syndrome (mucopolysaccharidosis II, MPS II);1 2 4 5 6 designated an orphan drug by FDA for use in this condition.3
Hunter syndrome is an X-linked recessive disease characterized by a deficiency of the lysosomal enzyme iduronate-2-sulfatase.1 2 4 4 5 6
In patients with Hunter disease, reduced or absent iduronate-2-sulfatase activity results in progressive accumulation of glycosaminoglycans in the lysosomes of various cells, leading to cellular engorgement, organomegaly, tissue destruction, and organ system dysfunction.1 5 6
Idursulfase improves endurance (measured by increases in walking distance) in patients with Hunter syndrome.1 2 4 5 6
Idursulfase Dosage and Administration
Administer by IV infusion.1
For solution compatibility and storage information, see Stability.
Administer by IV infusion using a 0.2-mcm filter.1
Do not infuse idursulfase infusions simultaneously through the same IV line with other drugs.1
Prior to infusion, dilute the appropriate dose of commercially available idursulfase concentrated solution (2 mg of the drug per mL) in 100 mL of 0.9% sodium chloride for injection according to the manufacturer’s instructions.1 Vials are for single use only; discard partially used vials of idursulfase solution.1
Withdraw the calculated volume providing the appropriate dose of idursulfase from the appropriate number of vials and dilute in 100 mL of 0.9% sodium chloride injection.1 Gently mix the solution in the infusion bag; do not shake.1 Consult the manufacturer’s labeling for additional information on dilution and administration of idursulfase.1
Rate of Administration
Administer by IV infusion at an initial infusion rate of 8 mL/hour for the first 15 minutes.1 May increase infusion rate in increments of 8 mL/hour every 15 minutes in order to administer the entire volume within the desired time, up to a maximum rate of 100 mL/hour.1 May administer the total volume of infusion in 1–3 hours; do not exceed 8 hours.1 May decrease infusion rate, temporarily discontinue infusion, or stop the infusion for the particular visit if infusion-related reactions occur.1
The specific activity of idursulfase is 41–77 units/mg, with 1 unit defined as the amount of activity that results in the hydrolysis of 1 mcmol of heparin disaccharide substrate per hour under specified assay conditions.1
Children ≥5 years of age: 0.5 mg/kg by IV infusion once weekly.1
0.5 mg/kg by IV infusion once weekly.1
Maximum infusion rate: 100 mL/hour.1
Maximum infusion rate: 100 mL/hour.1
No special population dosage recommendations at this time.1
Cautions for Idursulfase
The manufacturer states that there are no known contraindications to the use of idursulfase.1
Life-threatening hypersensitivity reactions (e.g., anaphylaxis, respiratory distress, hypoxia, hypotension, seizure, loss of consciousness, urticaria, angioedema of the throat and tongue) reported during and after idursulfase infusion in patients receiving the drug.1 5 Ensure that appropriate medical support measures are readily available during administration.1
Consider prolonged observation in patients who experience initial severe or refractory reactions, since biphasic anaphylactic reactions occurring up to approximately 24 hours after treatment and recovery from an initial anaphylactic reaction have been reported.1
Provide additional monitoring in patients with compromised respiratory function or acute respiratory disease, who may be at risk of serious acute exacerbation of their respiratory compromise secondary to infusion reactions.1 Consider delaying idursulfase infusion in patients with concomitant acute respiratory and/or febrile illness.1
If anaphylactic reactions or other severe allergic reaction occurs, immediately discontinue administration of the drug, and initiate appropriate medical treatment.1 In clinical studies, treatment included hospitalization, epinephrine, inhaled β-adrenergic agonists, and corticosteroids.1 4 5 Consider resuming the infusion at a slower rate or discontinuing the idursulfase infusion for that visit.1 May consider use of antihistamines and/or corticosteroids prior to and during subsequent infusions in patients who have experienced severe infusion reactions.1 4 5
Possible formation of antibodies to idursulfase.1 2 4 6 Increased incidence of infusion reactions, including allergic reactions, reported in patients who developed IgG antibodies to idursulfase; in addition, decreased reduction of urinary glycosaminoglycan excretion reported in patients who developed antibodies to idursulfase.1 The relationship between the development of antibodies to idursulfase and clinical efficacy outcome is not fully known.1
Not known whether idursulfase is distributed into milk.1 Use with caution.1
Patients ≥5 years of age have received idursulfase in clinical trials.1 Clinical response to idursulfase was similar in children, adolescents, and adults.1 Safety and efficacy of idursulfase in pediatric patients <5 years of age have not been established.1
No experience in patients ≥65 years of age; unknown whether geriatric patients respond differently than younger individuals.1
Common Adverse Effects
Pyrexia,1 2 headache,1 2 arthralgia,1 limb pain,1 pruritus,1 2 hypertension,1 malaise,1 visual disturbance,1 wheezing,1 abscess,1 chest wall musculoskeletal pain,1 2 musculoskeletal dysfunction,1 urticaria, 1 anxiety/irritability,1 2 atrial abnormality,1 dyspepsia,1 2 infusion site edema, injury,1 pruritic rash,1 2 skin disorder,1 superficial injury.1
In clinical studies, the most frequent serious adverse effects related to idursulfase were hypoxic episodes.1 The most common infusion-related reactions were headache, fever, cutaneous reactions, and hypertension.1 5
Interactions for Idursulfase
No formal drug interaction studies to date.1
AUC values increased in a greater than dose proportional manner following single 1-hour IV infusion of idursulfase dosages ranging from 0.15–1.5 mg/kg.1
Not known whether idursulfase is distributed into milk.1
Solution for IV Infusion
2–8°C; protect from light and do not shake or freeze.1 Vials are for single use only; discard any unused product.1
Administer diluted solution without delay; if not used immediately, diluted solution is stable at 2–8°C ≤48 hours.1 If held at room temperature, administer diluted solution within 8 hours.1
Biosynthetic (recombinant DNA origin) form of human iduronate-2-sulfatase, a lysosomal enzyme that catalyzes the hydrolysis of the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate in the lysosomes of various cell types.1 2 4 5 6 7
Provides an exogenous source of iduronate-2-sulfatase in patients with Hunter syndrome.1
Binds to mannose-6-phosphate receptors on the cell surface via mannose-6-phosphate residues on the oligosaccharide chains of the idursulfase molecule, which is then internalized and transported into lysosomes.1
Enzymatic activity of idursulfase, which results in catabolism of accumulated glycosaminoglycans, is dependent on the posttranslational modification of a specific cysteine to formylglycine.1
Advice to Patients
Importance of encouraging patients to participate in the Hunter Outcome Survey (http://www.elaprase.com or 866-888-0660) to understand the variability and progression of the disease and to continue to monitor and evaluate long-term treatment effects of idursulfase.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection, concentrate, for IV infusion
AHFS DI Essentials. © Copyright 2018, Selected Revisions September 1, 2010. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Shire Human Genetic Therapies, Inc. Elaprase (idursulfase) solution for intravenous infusion prescribing information. Cambridge, MA; 2007 Oct.
2. Muenzer J, Wraith JE, Beck M et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006; 8:465-73. [PubMed 16912578]
3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2007 Feb 26. From FDA website. Accessed 2007 Mar 13.
4. Muenzer J, Gucsavas-Calikoglu M, McCandless SE et al. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007; 90:329-37. [PubMed 17185020]
5. Muenzer J, Beck M, Eng CM et al. Multidisciplinary management of Hunter syndrome. Pediatrics.2009; 124 (suppl e):1228-39.
6. Okuyama T, Tanaka A, Suzuki Y et al. Japan Elaprase treatment (JET) study: idursulfase enzyme replacement therapy in adult patients with attenuated Hunter syndrome (Mucopolysaccharidosis II, MPS II). Mol Genet Metab. 2010; 99:18-25. [PubMed 19773189]
7. Manara R, Rampazzo A, Cananzi M et al. Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution.J inherit Metab Dis. 2010 Jan 6. (Epub ahead of print)
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- Drug class: lysosomal enzymes
Other brands: Elaprase